Identification of Fabry Disease in a Tertiary Referral Cohort of Patients with Hypertrophic Cardiomyopathy

Am J Med. 2018 Feb;131(2):200.e1-200.e8. doi: 10.1016/j.amjmed.2017.09.010. Epub 2017 Sep 21.

Abstract

Background: Fabry disease is an X-linked lysosomal storage disorder caused by the deficient activity of α-galactosidase A due to mutations in the GLA gene, which may be associated with increased left ventricular wall thickness and mimic the morphologic features of hypertrophic cardiomyopathy. Management strategies for these 2 diseases diverge, with Fabry disease-specific treatment utilizing recombinant α-galactosidase A enzyme replacement therapy.

Methods: We studied a prospectively assembled consecutive cohort of 585 patients (71% male) from 2 hypertrophic cardiomyopathy tertiary referral centers by screening for low α-galactosidase A activity in dried blood spots. Male patients with low α-galactosidase A activity levels and all females were tested for mutations in the GLA gene.

Results: In 585 patients previously diagnosed with hypertrophic cardiomyopathy, we identified 2 unrelated patients (0.34%), both with the GLA mutation encoding P.N215S, the most common mutation causing later-onset Fabry disease phenotype. These patients were both asymptomatic, a man aged 53 years and a woman aged 69 years, and demonstrated a mild cardiac phenotype with symmetric distribution of left ventricular hypertrophy. After family screening, a total of 27 new Fabry disease patients aged 2-81 years were identified in the 2 families, including 12 individuals who are now receiving enzyme replacement therapy.

Conclusions: These observations support consideration for routine prospective screening for Fabry disease in all patients without a definitive etiology for left ventriclar hypertrophy. This strategy would likely result, through cascade family testing, in the earlier identification of new Fabry disease-affected males and female heterozygotes who may benefit from monitoring and/or enzyme replacement therapy.

Keywords: Fabry disease; Genetic testing; Hypertrophic cardiomyopathy; Left ventricular hypertrophy.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cardiomyopathy, Hypertrophic / diagnosis
  • Cardiomyopathy, Hypertrophic / etiology*
  • Child
  • Child, Preschool
  • Diagnosis, Differential
  • Enzyme Replacement Therapy
  • Fabry Disease / complications
  • Fabry Disease / diagnosis*
  • Fabry Disease / drug therapy
  • Fabry Disease / genetics
  • Female
  • Genetic Testing
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Pedigree
  • Tertiary Healthcare*
  • Young Adult
  • alpha-Galactosidase / blood
  • alpha-Galactosidase / genetics
  • alpha-Galactosidase / therapeutic use

Substances

  • GLA protein, human
  • alpha-Galactosidase